Ibrutinib and Nivolumab in Treating Participants With Metastatic Solid Tumors

PRIMARY OBJECTIVES:

I. Evaluate the effect of the ibrutinib therapy on circulating levels of myeloid derived
suppressor cells MDSC.

SECONDARY OBJECTIVES:

I. Assess safety of the study combination in study subjects.

EXPLORATORY OBJECTIVES:

I. Evaluate the effect of the ibrutinib/nivolumab therapy on circulating levels of MDSC.

II. Evaluate the effect of the ibrutinib and ibrutinib/nivolumab therapy on the
immunosuppressive function of circulating MDSC by measuring their ability to inhibit T cell
proliferation and natural killer cell mediated antibody dependent cell cytotoxicity.

III. Study the effect of ibrutinib and ibrutinib/nivolumab therapy on levels of circulating
innate and adaptive immune cells such as natural killer cell and T lymphocyte subsets.

IV. Study circulating MDSC levels at the time of disease progression. V. Evaluate in a
preliminary fashion the effect of the regimen on progression-free survival.

OUTLINE:

Participants receive ibrutinib orally (PO) daily for 15 days. After 7 days receiving
ibrutinib, participants receive nivolumab intravenously (IV) over 60 minutes on days 1 and
15. Courses with nivolumab repeat every 28 days in the absence of disease progression or
unaccepted toxicity.

After completion of study treatment, participants are followed up every 3 months.

Inclusion Criteria:

- Patients with biopsy-proven metastatic solid tumor and be eligible to receive
nivolumab per standard of care

- Patients will be allowed to have any number of prior lines of therapy for metastatic
cancer

- Patients with measurable and non-measurable disease are allowed to participate

- Absolute neutrophil count (ANC) ? 1.5 x 10^3/mm^3

- Hemoglobin (Hgb) ? 9 g/dL

- Platelet count ? 100 x10^3/mm^3

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ? 2.5 x upper limit of
normal (ULN) or ? 5 x ULN in patients with liver metastases

- Prothrombin time ? 1.5 x ULN

- Total bilirubin ? 1.5 x ULN (unconjugated bilirubin of < 3 x ULN for patients with
known Gilbert syndrome)

- Creatinine clearance of ? 50 ml/min by Cockcroft-Gault equation

- Corrected QT interval of < 480 msec (using either Bazett?s or Fridericia's formula)

- Life expectancy of > 12 weeks

- Eastern Cooperative Oncology Group (ECOG) performance status 0 ? 2

- Sexually active women with child bearing potential must have a negative pregnancy test
obtained within 14 days prior to initiating study treatment

- Sexually active women of child-bearing potential and men must agree to use adequate
contraception prior to study entry, for the duration of study participation and for 3
months after completion of study treatment administration; adequate contraception
includes methods such as oral contraceptives, double barrier method (condom plus
spermicide or diaphragm), or abstaining from sexual intercourse

Exclusion Criteria:

- History of prior therapy with ibrutinib or nivolumab

- Unable to swallow capsules or having disease that is significantly affecting
gastrointestinal function and/or inhibiting small intestine absorption

- Diagnosis of congenital or acquired immunodeficiency with the exception of
chemotherapy induced immune suppression

- Active autoimmune disease requiring systemic treatment within the past 3 months or a
documented history of clinically severe autoimmune disease, or a syndrome that
requires systemic steroids of greater than or equal to prednisone 10 mg/day or other
immunosuppressive agents; patients with history of adequately treated Hashimoto?s
thyroiditis will be eligible; patients requiring a short course of a high dose
prednisone burst to treat asthma or common obstructive pulmonary disease will also be
eligible 5 days following completion of the prednisone treatment

- Use of systemic steroids at a dose above 10 mg/day of prednisone or prednisone
equivalent in cycle 1 of study therapy; systemic steroids must be discontinued at
least 5 days prior to initiating study therapy; exception will be given to patients
who develop immune related adverse events that necessitate use of steroids or other
immune suppressive agents; following cycle 1 of study treatment, the use of systemic
steroids will be allowed per discretion of the treating physician

- Active, non-infectious pneumonitis

- Ongoing or active infection requiring systemic therapy

- History of being positive for human immunodeficiency virus (HIV)

- History of hepatitis B or C

- History of receiving live vaccine within 30 days of planned start of study therapy

- Central nervous system (CNS) metastases or leptomeningeal carcinomatosis; patients
with history of adequately treated brain metastases that are stable for > 2 weeks
prior to the first dose of study regimen are eligible as long they no longer require
steroids and have no seizures or worsening focal neurologic symptoms; anti-epileptic
therapy will be allowed

- Patients who had prior systemic chemotherapy within 3 weeks (or < 5 half-lives ?
whichever is longer)

- Prior radiation therapy within 2 weeks of study enrollment

- Prior investigational therapy within 4 weeks

- Major surgery within 4 weeks or minor surgery within 2 weeks prior to the first dose
of study drug; port placement will not be considered major or minor surgery

- Any inter-current, uncontrolled systemic illness or any medical or psychiatric
condition that in the opinion of the investigator would make the study therapy unsafe
to the patient

- Unable to understand and sign informed consent form

- Uncontrolled, active cardiovascular disease including, but not limited to: symptomatic
congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York
Heart Association functional classification, unstable angina pectoris, cardiac
arrhythmia

- Any medications or substances that are strong inhibitors or inducers of CYP 3A4 need
to be discontinued prior to initiation the study therapy and for the duration of
ibrutinib treatment; patients can resume these medications 3 days after completion of
ibrutinib course

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition as ibrutinib or nivolumab